New local anesthetics with prolonged duration of action

目前的研究是为了开发比利多卡因作用时间更长且同样有效的新型局部麻醉剂。合成了三种侧链上分别含有甲酯（Li-Me）、乙酯（Li-Et）和丁酯（Li-Bu）的利多卡因衍生物。在体外研究了角膜反射抑制和迷走神经传导阻滞，以评价这些化合物的局部麻醉作用的起效和持续时间。去除的迷走神经传导阻滞的平均持续时间为32.5 min（利多卡因）、39.9 min（Li-Me）、68.2min（Li-Et）、108.7min(Li-Bu)，利多卡因与利多卡因酯衍生物的差异有统计学意义（Li-Ft、Li-Bu:p<0.001）。这些化合物持续时间的延长可能是由于理化性质（分配系数1.13，蛋白质结合89%）。这些利多卡因酯衍生物，尤其是利布，是长效局部麻醉剂，可用于长时间的外科手术、疼痛门诊和野区阻滞。

The Present study was made to develop new local anesthetic agents which work longer than lidocaine and are equally potent. Three lidocaine derivatives structurally with methyl ester(Li-Me), ethyl ester(Li-Et), or butyl ester (Li-Bu) in the side chain were synthesized. Corneal reflex suppression and conduction blockade in the vagus nerve,in vitro, were examined to evaluate the onset and duration of the local anesthetic effect of these compounds. The mean conduction blockades in the removed vagus nerve lasted 32.5 min(lidocaine),39.9 min(Li-Me),68.2min(Li-Et),and 108.7min(Li-Bu) and the differences between the lidocaine and lidocaine ester derivatives were statistically significant (Li-Ft and Li-Bu:p<0.001). The prolonged effect of duration of these compounds may be due to physiochemical properties (partition coefficient 1.13, protein binding 89%). These lidocaine ester derivatives, especially Li-Bu, are long acting local anesthetics and may be useful for prolonged surgical procedures, pain clinics,and field block.